甲胺酸脱酶介导的替代途径为甲胺素生物合成
Zizheng Guo1, Ying Zhou2, Jiangqi Li1
1Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou, 511443, China.
Nature communications
|April 24, 2025
概括
研究人员发现了二甲米辛酸脱酶 (AaDHAADH),一种能将二甲米辛酸 (AA) 转化为二甲米辛酸 (DHAA) 的酶. 这种酶能够在工程酵母中有效地新合成DHAA,为改进的艺术素 (ART) 生产铺平了道路.
科学领域:
- 生物技术是生物技术.
- 酶学 是一种酶学.
- 合成生物学 合成生物学
背景情况:
- 素 (ART) 是一种重要的抗疟疾药物.
- 甲酸 (AA) 是ART的前体,通过发酵产生.
- 从AA转化为ART的化学转化涉及二甲胺酸 (DHAA),但从AA转化为DHAA的直接酶途径缺失.
研究的目的:
- 为了识别和描述一种催化AA转化为DHAA的酶.
- 为了设计Saccharomyces cerevisiae用于新的DHAA生产.
- 为ART前体建立一个更有效的生物合成途径.
主要方法:
- 从Artemisia annua L.中克隆和表征二甲胺酸脱酶 (AaDHAADH).
- 网站导向的突变发生,以优化AaDHAADH活动 (P26L突变).
- 使用优化的基因,对Saccharomyces cerevisiae进行代谢工程,以生产DHAA.
主要成果:
- 鉴定了AADHAADH,催化了AA和DHAA之间的双向转换.
- 一个优化的突变 (P26L) 显示了对AA的2.82倍更高的活动.
- 在一个5升生物反应器中,工程S. cerevisiae产生了3.97g/L的DHAA.
结论:
- 发现AaDHAADH为DHAA合成提供了一个新的酶途径.
- 优化的AaDHAADH可以在酵母中有效地新生产DHAA.
- 这项研究提供了一种更方便,更有效的替代品,用于素生物合成.
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